Herophilus announced today the publication of “Neuroimmune Cortical Organoids Overexpressing C4A Exhibit Multiple Schizophrenia Endophenotypes” in bioRxiv, the preprint server for biology.
SAN FRANCISCO, CA – January 24, 2023 – Herophilus announced today the publication of “Neuroimmune Cortical Organoids Overexpressing C4A Exhibit Multiple Schizophrenia Endophenotypes” in bioRxiv, the preprint server for biology. The findings further demonstrate the emerging role the neuroimmune axis may play in the development of schizophrenia and in providing a platform for schizophrenia drug discovery.
The paper reports results from an ongoing research collaboration between Herophilus and Cerevel Therapeutics launched in December of 2021. The starting point for the research was Herophilus’ proprietary NICOTM (neuro-immune cerebral organoid) model which allows the study of neuroimmune interactions between microglia, neurons, and astrocytes in a realistic human tissue-like context. The NICOTM model is a component of the Herophilus Discovery Engine, which powers the use of human-derived, complex in vitro experiments for scaled, AI-driven drug discovery.
“Herophilus’ human neuroimmune organoid model helps to illuminate important insights into the complex biology of the human brain and the role microglia play in disease pathology. Our scientific collaboration with Herophilus has been a rewarding journey.” said Philip Iredale, Vice President, Biology, Cerevel Therapeutics.
“This collaboration is a great example of the commitment by a leading neuroscience company such as Cerevel to invest in cutting-edge approaches to develop potentially disease-modifying therapies for one of the most difficult and common brain diseases,” said Saul Kato, PhD, CEO of Herophilus. “The C4A NICOTM model built as part of this research collaboration can now potentially be used for the discovery of novel compounds that may prevent or reverse schizophrenia in patients, or for the discovery of biomarkers that may help detect the disease and track its progression before psychiatric symptoms manifest in a patient.”
There is a growing body of evidence implicating the neuroimmune system in the origin of schizophrenia and other complex brain diseases. Recent population-based genetics studies showed that higher levels of C4A correlate with increased schizophrenia risk. C4A is a key molecule of the complement pathway that is implicated in microglia-driven synaptic pruning. Thus, overexpression of C4A in the Herophilus NICOTM system was used to study the impact that a schizophrenia risk gene may have on the neuroimmune response.
The C4A NICOs were extensively profiled across several readouts of inflammation and neuroimmunological dysfunction. Several endophenotypes, biological markers of a disorder suspected to be part of the causal chain between genetic factors and ultimate patient symptoms, were observed in the C4A neuroimmune organoids. These included: modulation of inflammatory genes, release of secreted cytokines, and increased uptake of synapses by microglia.
About Herophilus
Herophilus is a San Francisco-based neurotherapeutics company focused on curing complex brain diseases. The company’s platform combines brain organoid science, systems neuroscience approaches, robotic automation, and advanced machine learning techniques to scale the ability to discover novel drugs for complex neurological and psychiatric diseases. In an industry-first approach, the company employs multi-modal phenotypic screening to discover characterizations of diseases never before achievable. These “deep phenotypes” are exploited to identify novel therapeutic targets and drug treatments for disorders for which current discovery techniques have proved least successful, including neurodevelopmental, psychiatric and neurodegenerative diseases. To learn more, visit www.herophilus.com.
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Jessica Sims